Although vasodilator therapy has proven to be an invaluable adjunct to the treatment of congestive heart failure, mechanisms by which this therapy improves tissue perfusion in acute and chronic congestive heart failure have not been clearly defined. It is commonly accepted that two major mechanisms are involved: reduction in arterial resistance and in ventricular volume or preload. The effect on ventricullr preload has been linked to the effects of these agents on venous capacitance. The known effects of these agents on augmenting venous capacitance and reducing venous return in the normal circulation would appear to be in contrast to their affects in the failing circulation where increases in cardiac output are normally observed. Indeed recent studies indicate that shifts in blood volume from the central to systemic circulation induced by vasodilator therapy play an important role in maintaining the venous return right atrial pressure relationship and thus cardiac output. The objective of the proposed studies is to delineate the acute and chronic effects of vasodilator therapy on venous return in chronic congestive heart failure. The effects of vasodilators on the venous return curve and blood volume will be examined in a right heart bypass preparation where both the venous return curve and changes in central blood volume can be quantitated in the normal systemic and splanchnic venous bed and in peparations subjected to long standing congestion. In chronic vasodilator therapy clinical studies have suggested tachyphylaxis to the beneficial effects of vasodilators may occur by unknown mechanisms. It will be the objective of the proposed chronic studies to: 1) define the homeostatic adjustments to chronic vasodilator therapy by quantifying central and systemic blood volume, peripheral resistance and renin level, 2) delineate the mechanism of fluid retetion and tachyphylaxis to some vasodilators and 3) delineate the long term effect on calculated wall stress and the stimulus to hypertrophy.